Osteogenesis imperfecta is a group of rare connective tissue disorders characterized by increased bone fragility and low bone mass. Affected individuals present a broad range of clinical severity, ranging from multiple fracturing in utero or perinatal death to normal adult stature and a low fracture incidence. The disorder is currently classified into seven types based on differences in clinical presentation and bone architecture. Osteogenesis imperfecta type I is the most common and the mildest form of the disorder.
Osteogenesis imperfecta congenita or type II osteogenesis imperfecta is the most severe form of the disease. Patients exhibit short limb dwarfism, thin skin, soft skull, unusually large fontanels (soft spots), blue sclera, whites of the eyes, small nose, low nasal bridge, inguinal hernia and numerous bone fractures at birth. There is bowing of limbs due to multiple fractures. More than 60% of affected infants die on the first day; and 80% die within the first week. Survival beyond the first year is exceedingly rare and usually involves intensive support such as continuous assisted ventilation. Death usually results from pulmonary insufficiency related to the small thorax, rib fractures, or flail chest due to lack of stable ribs.
Osteogenesis imperfecta is an autosomal dominant disorder caused by mutations in type I collagen genes - COL1A1 and COL1A2. COL1A1 and COL1A2 encode the alpha 1 and alpha 2 chains of the collagen triple helix, respectively. More than 250 different mutations in the COL1A1 and COL1A2 genes had been characterized. These alterations vary in type and location. The mild forms of osteogenesis imperfecta are usually caused by mutations that inactivate one allele of the COL1A1 gene, resulting in a reduced amount of normal type I collagen. The varied clinical characteristics of osteogenesis imperfecta reflect different classes of mutations in different regions of type I collagen genes.
